1. Field of the Invention
The mammalian capacity for producing immunoglobulins has found application in medicine and industry. The ability of immunoglobulins to distinguish specifically between chemical compounds of slightly differing structure has found broad application in the detection and measurement of a wide variety of compounds. In therapeutic applications, immunoglobulins can be administered to provide passive immunity against diseases. Major stumbling blocks in the wide application of immunoglobulin therapy were the heterogeneity of antisera and the limited availability of human antisera for a specific antigen.
The seminal discovery by Kohler and Milstein of mouse "hybridomas" capable of secreting specific monoclonal antibodies against predefined antigens ushered in a new era in experimental immunology. Many of the problems associated with antisera are circumvented; the clonal selection and immortality of such hybridoma cell lines assure the monoclonality and permanent availability of their antibody products. At the clinical level, the use of such antibodies is clearly limited by the fact that they are foreign proteins and would act as antigens to humans.
Human cells have only been difficulty cultured in vitro. Efforts to achieve a human hybridoma which is a cross between a lymphoid cell and a myeloma cell have heretofore been unsuccessful. The problems of maintaining a stable culture of human cells have inhibited the ready production of human-human hybridomas.
2. Description of the Prior Art
The production of mouse hybridomas is described by Kohler, G. and Milstein, K. (1975) Nature 356: 495-7; (1976) Euro. J. Immunol 6: 511-519. Chimeric hybridomas generated by fusing mouse myeloma cells with human immunoglobulin-producing cells is described by Levy, R. and Dilley, I. (1978) PNAS USA 75: 2111-2415. Permanent cultures of specific antibody-producing human B-lymphocytes obtained by transformation with Epstein-Barr virus is described by Steinitz, M. (1977) Nature 269: 420-422 .